A5038912895- Receptor Mechanisms and Signaling
- Synthesis and Characterization of Heterocyclic Compounds
- Neuropeptides and Animal Physiology
- Drug Transport and Resistance Mechanisms
- Stress Responses and Cortisol
- Trace Elements in Health
- Adenosine and Purinergic Signaling
- Enzyme Structure and Function
- Synthesis of Tetrazole Derivatives
- Sleep and Wakefulness Research
- Click Chemistry and Applications
- Pharmacological Receptor Mechanisms and Effects
- Quinazolinone synthesis and applications
- Radioactive element chemistry and processing
- Phenothiazines and Benzothiazines Synthesis and Activities
- Synthesis and Biological Evaluation
- Hormonal Regulation and Hypertension
- Enzyme Production and Characterization
- Monoclonal and Polyclonal Antibodies Research
- Pharmacological Effects and Toxicity Studies
- Metal Extraction and Bioleaching
- Chemical Synthesis and Characterization
- Porphyrin Metabolism and Disorders
- Peptidase Inhibition and Analysis
- Endoplasmic Reticulum Stress and Disease
United States Military Academy
2017-2025
Merck & Co., Inc., Rahway, NJ, USA (United States)
2022
Heptares Therapeutics (United Kingdom)
2011-2015
University of Hertfordshire
2012
ETH Zurich
2007-2009
University of Chicago
2007
University of Zurich
2005
Potent, ligand efficient, selective, and orally efficacious 1,2,4-triazine derivatives have been identified using structure based drug design approaches as antagonists of the adenosine A(2A) receptor. The X-ray crystal structures compounds 4e 4g bound to GPCR illustrate that molecules bind deeply inside orthosteric binding cavity. In vivo pharmacokinetic efficacy data for compound 4k are presented, demonstrating potential this series treatment Parkinson's disease.
Abstract Narcolepsy type 1 (NT1) is a chronic neurological disorder that impairs the brain’s ability to control sleep-wake cycles. Current therapies are limited management of symptoms with modest effectiveness and substantial adverse effects. Agonists orexin receptor 2 (OX R) have shown promise as novel therapeutics directly target pathophysiology disease. However, identification drug-like OX R agonists has proven difficult. Here we report cryo-electron microscopy structures active-state...
BtuCD is an adenosine triphosphate-binding cassette (ABC) transporter that translocates vitamin B12 from the periplasmic binding protein BtuF into cytoplasm of Escherichia coli. The 2.6 angstrom crystal structure a complex BtuCD-F reveals substantial conformational changes as compared with previously reported structures and BtuF. lobes are spread apart, displaced pocket. transmembrane BtuC subunits reveal two distinct conformations, translocation pathway closed to both sides membrane....
A novel, highly diastereoselective, and metal-free synthesis of multisubstituted piperidines via an SN1 approach is reported in this study. The method allows for the preparation functionalized compounds with exceptional diastereomeric selectivities consistently reproducible yields. These are significant interest due to their remarkable biological activities toward influenza endonuclease.
Although current antiretroviral therapy can control HIV-1 replication and prevent disease progression, it is not curative. Identifying mechanisms that lead to eradication of persistent viral reservoirs in people living with (PLWH) remains an outstanding challenge achieving cure. Utilizing a phenotypic screen, we identified novel chemical class capable killing infected peripheral blood mononuclear cells. Tool compounds ICeD-1 ICeD-2 ("inducer cell death-1 2"), optimized for potency...
The structural analysis of class B G protein-coupled receptors (GPCR), cell surface proteins responding to peptide hormones, has until recently been restricted the extracellular domain (ECD). Corticotropin-releasing factor receptor type 1 (CRF1R) is a mediating stress response and also considered drug target for depression anxiety. Here we report crystal structure transmembrane human CRF1R in complex with small-molecule antagonist CP-376395 hexagonal setting translational...
Recent technical advances have greatly facilitated G-protein coupled receptors crystallography as evidenced by the number of successful x-ray structures that been reported recently. These include novel detergents, specialised techniques well protein engineering solutions such fusions and conformational thermostabilisation. Using thermostabilisation, it is possible to generate variants GPCRs exhibit significantly increased stability in detergent micelles whilst preferentially occupying a...
We compare aspects of biological X-ray absorption spectroscopy (XAS) studies cations and anions, report on some examples anion binding in systems. Brown algae such as Laminaria digitata (oarweed) are effective accumulators I from seawater, with tissue concentrations exceeding 50 mM, the vanadate-containing enzyme haloperoxidase is implicated halide accumulation. have studied chemical state iodine its role at K edge, bromoperoxidase Ascophyllum nodosum (knotted wrack) Br edge. Mo essential...